Short Methionine Synthases

Although most organisms synthesize methionine from homocysteine and 5-methyltetrahydrofolate, we propose that many bacteria and archaea use alternative enzymes that rely on other methyl donors. These methionine synthases are homologous to MetE, which uses 5-methyltetrahydrofolate, but they lack the N-terminal folate-binding domain of MetE. We describe four families of short MetE-like methionine synthases that are distantly related to each other (under 30% amino acid identity). The first family, MesA, is found only in methanogens, and was previously shown to be a methionine synthase . It is thought to obtain methyl groups from corrinoid (vitamin B12-binding) proteins. We describe two additional families, MesB and MesC, that are found only in anaerobic organisms that have the Wood-Ljungdahl pathway. We propose that most of these proteins obtain methyl groups from that pathway. The final family, MesD, is found only in aerobic bacteria and genetic data suggests that it does not use 5-methyltetrahydrofolate as a methyl donor. We propose that MesD obtains its methyl groups from an uncharacterized protein family (DUF1852).